Innate Host Defense of the Lung: Effects of Lung-lining Fluid pH

Abstract

Lung-lining fluid (LLF) is a primary constituent of the pulmonary host defense system. It is distributed continuously throughout the respiratory tract but is heterogeneous regarding its chemistry and physiology between the conducting airways and alveoli. The conducting airways are lined with airway surface liquid (ASL), a mucus gel-aqueous sol complex that interacts functionally with epithelial cilia as the mucociliary escalator. The alveoli are lined with alveolar subphase fluid (AVSF) and pulmonary surfactant. AVSF sterility is maintained in part by the phagocytic activity of resident alveolar macrophages. Normal ASL and AVSF are both more acidic than blood plasma. However, the details of acid-base regulation differ between the two media. Appreciable transepithelial acid-base flux is possible across the airway epithelium, whereas the alveolar epithelium is relatively impermeable to transepithelial acid-base flux. Moreover, one must consider the influence of resident macrophages on AVSF pH. Resident macrophages occupy a sizable fraction of AVSF by volume and are a substantial source of metabolic H+. The buffering capacities of ASL and AVSF probably are largely due to secreted peptides (e.g., ASL mucins and AVSF surfactant proteins). Acid-base exchange between the extracellular hydrophase and intracellular buffering systems of resident macrophages represents an additional buffer pool for AVSF. The pH of ASL and AVSF can be depressed by disease or inflammation. Low pH is predicted to suppress microbe clearance from the airways and alveoli, increase pathogen survival in both regions, and alter mediator release by resident macrophages and recruited leukocytes thereby increasing the propensity for bystander cell injury. Overall, ASL/AVSF pH is expected to be a major determinant of lung host defense responses.

Acidosis Potentiates the Host Proinflammatory Interleukin-1β Response to Pseudomonas aeruginosa Infection

“…4 (20, 21). Relevant to our studies, this is observed during bacterial infection, where anaerobic glycolysis, lactic acid accumulation, hypoxia, bacterial fatty acids, and hypochlorous acid (HOCl) production by activated neutrophils contribute to local acidosis with measured pH values ranging from 5.9 to 7.0, depending upon the disease process and method of measurement (22)(23)(24)(25)(26)(27). In CF, the loss of CF transmembrane conductance regulator (CFTR)-mediated bicarbonate transport has been proposed to contribute to pulmonary acidosis, which is supported by pH measurements of airway surface liquid, submucosal gland fluid, and mucopurulent airway secretions that range from ϳ6.1 to 6.9 (28)(29)(30)(31)(32)(33).…”

Hag Mediates Adherence ofMoraxella catarrhalisto Ciliated Human Airway Cells

“…Although all of these cell types are relevant to the diseases caused by M. catarrhalis, they lack important aspects of the pathogen-targeted mucosa, such as the features of cilia and mucociliary activity. The ciliated cells of the respiratory tract and other mucosal membranes keep secretions moving out of the body so as to assist in preventing colonization by invading microbial pathogens (10,26,71,91). Given this critical role in host defense, it is interesting to note that a few bacterial pathogens target ciliated cells for adherence, including Actinobacillus pleuropneumoniae (32), Pseudomonas aeruginosa (38, 108), Mycoplasma pneumoniae (58), Mycoplasma hyopneumoniae (44, 45), and Bordetella species (5,62,85,101).…”

Endoscopic sensing of alveolar pH

“…This has led to conjecture about the consequences of inflammation and disease on pH in the AVSF [1]. The work presented here focused on developing a robust engineering platform to provide an approach for measuring alveolar pH.…”

“…In the lung, a thin film of airway surface liquid lines the air-facing surface of the lungs. The conducting airways are lined with a mucus gel-aqueous sol complex of up to 100 microns in depth called air surface liquid (ASL) whilst the alveolar regions are lined with a complex of alveolar subphase fluid (AVSF) and pulmonary surfactant [1]. ASL pH is acidic compared to blood pH and in vivo in healthy humans ASL has been recorded as 6.6 using a bronchoscopically-deployed pH electrode [2].…”

“…ASL pH is acidic compared to blood pH and in vivo in healthy humans ASL has been recorded as 6.6 using a bronchoscopically-deployed pH electrode [2]. In preclinical models, the ASL pH has been measured to be between 6.8 and 7.1 [3] and has also been shown to be responsive to changes to blood pH as well as to apical challenges of acid and alkali [1,4]. In contrast, current understanding of the AVSF is limited by the technological hurdles of measuring pH in the distal lung.…”